EAL

CD: Bone Density (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine the relationship between celiac disease and bone mineral density with rigorous control for potential confounding variables including menopausal age, BMI, hysterectomy, and exposure to HRT.

Inclusion Criteria:

Histologically proven celiac disease and registered with the Dept of Gastroenterology at Hull Royal Infirmary.

Exclusion Criteria:

Not specifically mentioned.

Description of Study Protocol:

Recruitment

All patients registered on the database of the Dept of Gastroenterology at Hull Royal Infirmary invited to attend Princess Royal Hospital for densitometric exam of spine and hip.

Design

Cross-sectional study.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Bone densitometry and clinical questionnaire.

Statistical Analysis

Two sided tests were used with the level of significance set at 0.05. Parametric variables were compared using the t test (ANOVA and paired t test) and non-parametric variables were compared using the chi-square test, or Fisher's exact test where the numbers were too small to allow accurate interpretation of the chi-square test. Multiple regression analysis was performed to test the effect of BMI, menopausal age, adherence to diet, and duration of celiac disease on BMD. All values are stated as mean (SD).

Data Collection Summary:

Timing of Measurements

Patients approached by letter advising them of potential risk for osteoporosis and inviting them to undergo bone densitometry. Subjects also given a clinical questionnaire.

Dependent Variables

Bone densitometry: DEXA at lumbar spine and femoral neck
Weight, height, BMI

Independent Variables

Gluten-free diet and degree of dietary adherence
Time since diagnosis
Factors influencing BMD: smoking, alcohol use, exercise, drug therapy including HRT, corticosteroids, prior hysterectomy

Control Variables

Description of Actual Data Sample:

Initial N: 135 female celiac patients

Attrition (final N): 81 registered women (60%) and control subjects matched for height, weight, menopausal status. Postmenopausal patients further matched to controls of equivalent menopausal age.

Age: Postmenopausal: mean age 59.2 +/- 8.6 years (range 40 - 77)

Ethnicity: Not mentioned

Other relevant demographics: 52 were premenopausal and 29 post-menopausal. Age at diagnosis of celiac disease and institution of a gluten-free diet ranged from 0 - 41 years, median of 8 years.

Anthropometrics: No differences between groups with respect to hysterectomy, exposure to HRT, corticosteroids, exercise, or tobacco and alcohol consumption.

Location: Kingston Upon Hull

Summary of Results:

	Celiacs	Controls	P value
Overall	n=81	n=81
L2 - L4	1.076 +/- 0.186	1.155 +/- 0.143	< 0.001
Femoral Neck	0.887 +/- 0.142	0.965 +/- 0.127	< 0.001
Postmenopausal	n=29	n=29
L2 - L4	0.924 +/- 0.14	1.129 +/- 0.18	< 0.001
Femoral Neck	0.785 +/- 0.10	0.885 +/- 0.11	< 0.001
Premenopausal	n=52	n=52
L2 - L4	1.160 +/- 0.151	1.169 +/- 0.117	NS
Femoral Neck	0.943 +/- 0.129	1.010 +/- 0.114	< 0.001

Other Findings

58 patients reported that they had always adhered to a gluten-free diet, 17 patients usually adhered, and 6 patients never adhered.

In celiac patients, bone mineral density was significantly lower at the lumbar spine than in controls (1.076 +/- 0.186 vs 1.155 +/- 0.143, p < 0.001) and at the femoral neck as well (0.887 +/- 0.142 vs 0.965 +/- 0.127, p < 0.001).

When the celiac patients were stratified by menopausal status, it was found that postmenopausal patients (n=29) had significantly lower spinal bone mineral density than controls (0.924 +/- 0.14 vs 1.129 +/- 0.70, p < 0.001) and femoral neck bone mineral density also (0.785 +/- 0.72 vs 0.885 +/- 0.55, p < 0.001).

Premenopausal patients (n=52) did not show significantly different spinal bone mineral density compared to controls, but at the femoral neck, differences were significantly different (0.943 +/- 0.129 vs 1.010 +/- 0.114, p < 0.01).

The age at diagnosis of celiac disease and adherence to a gluten-free diet did not exert a significant influence on bone mineral density at either hip or spine.

BMI was positively correlated with spinal but not femoral neck bone mineral density (p < 0.01) and menopausal age correlated significantly with both spinal and femoral neck bone mineral density (p < 0.001).

Author Conclusion:

This study confirms that celiac disease adversely affects bone mineral density, and that the relationship holds when female celiac patients are compared with strictly selected controls matched for sex, height and weight, menopausal status and menopausal age. Celiac disease should be added to the list of medical conditions which constitute an indication for bone densitometry in order that the individual risk of osteoporosis-related fracture may be determined.

Funding Source:

University/Hospital:

Princess Royal Hospital (UK), Hull Royal Infirmary (UK)

Reviewer Comments:

Strictly-matched controls. 60% response rate, what about other 40%? Relationships between adherence and bone density measurements could have also been investigated.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		???
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	???
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	Yes
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	Yes
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		???
	4.1.	Were follow-up methods described and the same for all groups?	???
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	???
	4.4.	Were reasons for withdrawals similar across groups?	???
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		N/A
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes